S278: CEREBRAL HEMODYNAMICS AND OXYGEN METABOLISM IN PATIENTS WITH MILD AND SEVERE SICKLE CELL DISEASE AND THALASSEMIA
Authors: Liza Afzali-Hashemi, Koen P. A. Baas, Anouk Schrantee, Erfan Nur, Chau Vu, Soyoung Choi, Silvie Suriany, John C. Wood, Aart J. Nederveen, Bart J. Biemond
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is complicated by cerebral infarctions. These include silent cerebral infarcts (SCIs) which can be found in 40% of the patients by the age of 20 years and progress further with age. Studies in patients with severe (HbSS and HbSβ0) SCD have reported reduced oxygen metabolism compared to controls despite the preserved oxygen delivery (OD). Whereas previous studies have found similar lesion load in mild SCD patients (HbSC and HbSβ+), cerebral oxygen metabolism has not been studied in this group forming almost 30% of the SCD patients. In this study, we investigated the differences between milder and severe SCD patients by comparing parameters of cerebral hemodynamics and oxygen metabolism between different anemic groups. Aims: We aimed to assess the cerebral blood flow (CBF), OD, cerebral oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and SCI volumes in adult patients with severe and milder SCD and compared these results with thalassemia patients (as anemic control) and healthy controls. In addition, the effect of a vasodilatory stimulus on the cerebral parameters was studied to test if increased CBF influences cerebral oxygen consumption. Methods: Venous blood T2 was measured in the superior sagittal sinus using T2-Relaxation-Under-Spin-Tagging (TRUST). White matter (WM) and gray matter (GM) CBF were measured using time-encoded pseudo-continuous ASL (te-ASL). TRUST and te-ASL scans were performed before and after acetazolamide (ACZ) administration as a vasodilatory stimulus. Fluid-Attenuated Inversion Recovery (FLAIR) scans were acquired for the assessment and segmentation of SCIs. OEF was calculated from arterial saturation measured by pulse oximetry and venous saturation calculated from TRUST-derived venous blood T2. Subsequently, CMRO2 was calculated by multiplying CBF, OEF, and oxygen content (calculated from hemoglobin and arterial saturation). To test the effect of ACZ-induced vasodilation, ∆CBF, ∆OD, ∆OEF, and ∆CMRO2 were calculated. Results: In this study, 75 patients with severe SCD, 26 patients with mild SCD, 18 patients with thalassemia (7 NTDT and 11 TDT) and 30 healthy controls were included. WM and GM CBF were significantly higher in severe SCD and thalassemia patients compared to mild SCD patients and healthy controls (Table 1). OEF was significantly lower in severe SCD patients compared to other groups and significantly lower in thalassemia patients compared to mild SCD patients and healthy controls. CMRO2 was significantly lower in severe SCD and thalassemia patients compared to mild SCD patients and healthy controls (Table 1). ACZ administration reduced the CMRO2 in severe SCD patients compared to the other groups (Table 1). SCI volume was significantly larger in the severe SCD group compared to the healthy controls but did not differ between the other groups (Table 1). Summary/Conclusion: This study demonstrated that severe SCD and thalassemia patients have reduced cerebral oxygen consumption, which is most likely associated with the severity of anemia. Conversely, mild SCD patients showed a more balanced oxygen supply versus demand, even though they had similar SCI volumes. This suggests that the pathophysiology of SCIs in mild SCD may not be solely driven by anemia and that more sickle cell-specific aspects like reduced RBC deformability and higher viscosity, may contribute. Notably, we found that elevated CBF induced by ACZ reduced CMRO2 in severe SCD patients, indicating that functional shunting may be a contributing factor in the more severe cases of SCD.Keywords: Sickle cell anemia, Sickle cell disease, Thalassemia, Hemoglobinopathy